Evolutionary Relationship Between Translation Initiation Factor eIF-2γ and Selenocysteine-Specific Elongation Factor SELB: Change of Function in Translation Factors

1998 ◽  
Vol 47 (6) ◽  
pp. 649-655 ◽  
Author(s):  
Patrick J. Keeling ◽  
Naomi M. Fast ◽  
Geoff I. McFadden
Keyword(s):  
Translation Initiation ◽  
Evolutionary Relationship ◽  
Elongation Factor ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Translation Factors ◽  
Specific Elongation

scholarly journals Inhibition of eEF2K synergizes with glutaminase inhibitors or 4EBP1 depletion to suppress growth of triple-negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
YoungJun Ju ◽  
Yaacov Ben-David ◽  
Daniela Rotin ◽  
Eldad Zacksenhaus
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Translation Initiation ◽  
Triple Negative ◽  
Elongation Factor ◽  
Protein Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Related Factors ◽  
Metabolic Conditions

AbstractThe eukaryotic elongation factor-2 kinase, eEF2K, which restricts protein translation elongation, has been identified as a potential therapeutic target for diverse types of malignancies including triple negative breast cancer (TNBC). However, the contexts in which eEF2K inhibition is essential in TNBC and its consequences on the proteome are largely unknown. Here we show that genetic or pharmacological inhibition of eEF2K cooperated with glutamine (Gln) starvation, and synergized with glutaminase (GLS1) inhibitors to suppress growth of diverse TNBC cell lines. eEF2K inhibition also synergized with depletion of eukaryotic translation initiation factor 4E-binding protein 1 (eIF4EBP1; 4EBP1), a suppressor of eukaryotic protein translation initiation factor 4E (eIF4E), to induce c-MYC and Cyclin D1 expression, yet attenuate growth of TNBC cells. Proteomic analysis revealed that whereas eEF2K depletion alone uniquely induced Cyclin Dependent Kinase 1 (CDK1) and 6 (CDK6), combined depletion of eEF2K and 4EBP1 resulted in overlapping effects on the proteome, with the highest impact on the ‘Collagen containing extracellular matrix’ pathway (e.g. COL1A1), as well as the amino-acid transporter, SLC7A5/LAT1, suggesting a regulatory loop via mTORC1. In addition, combined depletion of eEF2K and 4EBP1 indirectly reduced the levels of IFN-dependent innate immune response-related factors. Thus, eEF2K inhibition triggers cell cycle arrest/death under unfavourable metabolic conditions such as Gln-starvation/GLS1 inhibition or 4EBP1 depletion, uncovering new therapeutic avenues for TNBC and underscoring a pressing need for clinically relevant eEF2K inhibitors.

scholarly journals In silico analysis of bacterial translation factors reveal distinct translation event specific pI values

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Soma Jana ◽  
Partha P. Datta
Keyword(s):  
Translation Initiation ◽  
In Silico ◽  
Bacterial Species ◽  
Amino Acid Sequences ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Release Factors ◽  
Translation Factors ◽  
70S Ribosome ◽  
Bacterial Translation

Abstract Background Protein synthesis is a cellular process that takes place through the successive translation events within the ribosome by the event-specific protein factors, namely, initiation, elongation, release, and recycling factors. In this regard, we asked the question about how similar are those translation factors to each other from a wide variety of bacteria? Hence, we did a thorough in silico study of the translation factors from 495 bacterial sp., and 4262 amino acid sequences by theoretically measuring their pI and MW values that are two determining factors for distinguishing individual proteins in 2D gel electrophoresis in experimental procedures. Then we analyzed the output from various angles. Results Our study revealed the fact that it’s not all same, or all random, but there are distinct orders and the pI values of translation factors are translation event specific. We found that the translation initiation factors are mainly basic, whereas, elongation and release factors that interact with the inter-subunit space of the intact 70S ribosome during translation are strictly acidic across bacterial sp. These acidic elongation factors and release factors contain higher frequencies of glutamic acids. However, among all the translation factors, the translation initiation factor 2 (IF2) and ribosome recycling factor (RRF) showed variable pI values that are linked to the order of phylogeny. Conclusions From the results of our study, we conclude that among all the bacterial translation factors, elongation and release factors are more conserved in terms of their pI values in comparison to initiation and recycling factors. Acidic properties of these factors are independent of habitat, nature, and phylogeny of the bacterial species. Furthermore, irrespective of the different shapes, sizes, and functions of the elongation and release factors, possession of the strictly acidic pI values of these translation factors all over the domain Bacteria indicates that the acidic nature of these factors is a necessary criterion, perhaps to interact into the partially enclosed rRNA rich inter-subunit space of the translating 70S ribosome.

scholarly journals In silico analysis of bacterial translation factors reveal distinct translation event specific pI values

2020 ◽  
Author(s):  
SOMA JANA ◽  
Partha Pratim Datta
Keyword(s):  
Translation Initiation ◽  
In Silico ◽  
Bacterial Species ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Acidic Property ◽  
Release Factors ◽  
Translation Factors ◽  
70S Ribosome ◽  
Bacterial Translation

Abstract Background Protein synthesis is a cellular process that takes place through the successive translation events within the ribosome with the help of the event-specific protein factors, namely, initiation, elongation, release, and recycling factors. The translation process is fundamental to all organisms living in the wide variety of environments. In this regard, we asked the questions about how similar are those translation factors to each other from a wide variety of bacteria? Hence, we did a thorough in silico study of the translation factors from 495 bacterial sp., and 4262 amino acid sequences, wherein we theoretically measured their pI and MW values that are the two determining factors for distinguishing individual proteins in 2D gel electrophoresis. Then we analyzed the output from various angles. Results Our study revealed that, not all the pI values are same or random, but there is a distinct order, such that the pI values of translation factors are translation event specific. We found that the translation initiation factors are mainly basic, whereas, elongation and release factors that interact with the inter-subunit space of the intact 70S ribosome during translation are strictly acidic. Further analysis revealed that the acidic property of those factors is due to the higher frequencies of glutamic acids. However, two translation factors, the translation initiation factor 2 (IF2) and the ribosome recycling factor (RRF) showed variable pI values. Remarkably, the variability of the pI values of these two factors showed distinct lineage with the order of phylogeny. Conclusion From our results we conclude that, among all the bacterial translation factors, elongation and release factors are more conserved in terms of their pI values in comparison to initiation and recycling factors. Acidic properties of these factors are independent of habitat, nature, or the phylogeny of the bacterial species. Furthermore; irrespective of the different shapes, sizes, and functions of the elongation and release factors, possession of their strictly acidic pI values indicate that the acidic nature of these factors is a necessary criterion, perhaps to interact into the partially enclosed rRNA rich inter-subunit space of the translating 70S ribosome.

scholarly journals Interplay of Methionine tRNAs with Translation Elongation Factor Tu and Translation Initiation Factor 2 inEscherichia coli

1996 ◽  
Vol 271 (37) ◽  
pp. 22321-22325 ◽  
Author(s):  
Jean-Michel Guillon ◽  
Senta Heiss ◽  
Julie Soutourina ◽  
Yves Mechulam ◽  
Soumaya Laalami ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Elongation Factor ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Elongation Factor Tu ◽  
Inescherichia Coli ◽  
Translation Elongation Factor ◽  
Translation Elongation ◽  
Initiation Factor 2 ◽  
Translation Initiation Factor 2
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